During the Korean War, Coe worked as a CIA case officer; as a part of a front organization, Western Enterprises, in Taiwan; the CIA's efforts at the time were intended to counter influences and actions of Mao's China in Asia.[3]

He has authored a number of popular works for the non-specialist audience, several of which have been best-selling and much reprinted, such as The Maya (1966) and Breaking the Maya Code (1992). He also co-authored the book Mexico: From the Olmecs to the Aztecs (1962, sixth edition, 2008) with Rex Koontz.

Coe is considered, by most scholars of Mesoamerica and the Maya,[who?] to have done foundational work in three areas: 1) in his Harvard dissertation, at La Victoria, Guatemala, he established the first secure chronology of ceramics for southern Mesoamerica and which has served, almost without revision, to anchor chronologies elsewhere in Mesoamerica and the Maya world[citation needed]; 2) from his work (with Richard Diehl) at San Lorenzo Tenochtitlan, Veracruz, Mexico and employing the then new technology of magnetometry to locate and salvage most of the Olmec colossal heads now known, he greatly expanded knowledge of the Olmec civilization such that he is considered one of the discoverers of the Olmec[citation needed]; 3) against the very public rebukes of the then reigning doyen of Maya archaeology, J. E. S. Thompson, Coe championed Yuri Knorosov and the phonetic decipherment of Maya writing, and set about solving what was then the greatest research problem for the Maya, decipherment of Maya writing, along with his own fundamental discoveries, by stimulating and inspiring his Yale University students Peter Mathews and Karl Taube to great breakthroughs; another student, Stephen Houston, became co-author of many of the papers with them and with the greatest epigrapher of the day, David Stuart; Coe also provided insights and guidance to Floyd Lounsbury, noted anthropological linguist at Yale, and to the authors of the acclaimed The Blood of Kings, a work about Classic Maya rulership, Mary Ellen Miller, at Yale, and Linda Schele, at the University of Texas at Austin, the latter who was also a central figure in Maya epigraphy for most of the 1970s and 1980s; Coe’s Breaking the Maya Code (1992), which was nominated for a National Book Award, relates the story.

Coe was, also, the first to date El Baúl Stela 1 correctly (Coe 1957; cf. Parsons 1986:61); this sculpture from the Southern Maya Area (SMA) is one of three known with Cycle 7 Long Count dated monuments; since then, that it predated all Lowland Long-Count dated sculpture was not questioned. He also, with Kent Flannery, was the first to observe that the greatest southern area site, Kaminaljuyu, probably profited greatly from its proximity to and exploitation of the enormous El Chayal obsidian fields. Coe's own discovery of the Primary Standard Sequence, a sequence of hieroglyphs appearing around the rim of many Classic Maya ceramic vessels, and also of the fourth Maya codex still in existence, in themselves would have secured a place in the history of Maya research. Finally, his many insights, dropped casually to his students or written up in short reports, including that the Popol Vuh was but a fragment of a great lost pan-Maya mythology, and that Classic Maya rulers were shamanic figures as well as administrators, exemplify how he has been the singular leader of research in Mesoamerica and the Maya, and one of a handful of general figures in archaeology as a whole throughout the 1960s and even to today to rank with the founders of the discipline of anthropology. Considering everything, to many other scholars, researchers and students, such are his achievements that they warrant labeling the period from the 1960s almost until today as "the Coe Epoch."

In addition to many seminal publications about Mesoamerica and the Maya, Coe contributed several key papers outside of his own specialized foci, including “The Churches on the Green,” which, during the height of the “New Archaeology,” succinctly pointed out how processualism failed.[citation needed] Indicative of the wide range and breadth of his intellect, his book on the Angkor civilization of ancient Cambodia, "Angkor and the Khmer Civilization (Ancient Peoples and Places)" (Thames and Hudson) is considered the best single volume on the subject,[who?] following up on an early comparative interest.

Coe has added qualified support to the "Cultura Madre" view of the Olmec as the "mother culture of Mesoamerican civilization"; another issue, use of information obtainable from looted Maya ceramics, has brought criticism. Recently, some of Coe's work has come under scrutiny by two scholars of Pre-Columbian art. His work on, for example, the Cascajal Block[7] and on the Wrestler,[8] has been called into question. Other scholars dispute these claims and find them inadequately supported by evidence. The Cascajal block in particular is argued to have many features fully consistent with Olmec imagery,[9][10] and the same has been said for the Wrestler.[11][12][13] Nevertheless, such criticisms are based on what other scholars consider poorly or undefined notions of Olmec iconography and of rulership.

During the course of his lengthy scientific career, Coe has been the recipient of a number of awards in recognition of his substantial contributions to the fields of archaeology and anthropology. These include:

^Freidel, David, and F. Kent Reilly III. 2010. The flesh of God, cosmology, food, and the origins of political power in southeastern Mesoamerica" in Pre-Columbian Foodways: Interdisciplinary Approaches to Food, Culture, and Markets in Mesoamerica edited by John E. Staller and Michael D. Carrasco. pp. 635–680. Springer.